Department of Pharmacology, Center for Pharmacology and Experimental Therapeutics, Ernst-Moritz-Arndt University, Greifswald, Germany.
Int J Obes (Lond). 2011 Mar;35(3):364-72. doi: 10.1038/ijo.2010.158. Epub 2010 Aug 24.
Risk alleles of the fat mass- and obesity-associated gene (FTO) are related not only to increased body mass index (BMI) values but also to mortality. It was speculated that cellular effects of the FTO gene affect most organs, especially their ability to maintain or regenerate proper function when afflicted by various diseases. FTO is highly expressed in the hypothalamus and also in the pituitary gland. The decrease in growth hormone (GH) secretion is known to cause a decrease in lean body mass in older subjects.
We hypothesized an association of rs9926289 with insulin-like growth factor (IGF)-I.
Cross-sectional data from the Study of Health in Pomerania, a population-based study in the northeastern part of Germany, were used.
For the final analyses, 3882 subjects aged 20-79 years were available.
Continuous IGF-I, low IGF-I according to clinically meaningful age- and gender-specific reference values, and BMI were used as outcome measures.
Over all age groups, a statistically significant relationship between FTO and IGF-I was found. In subjects younger than 55 years of age, homozygous carriers of the FTO risk allele exhibited lower serum IGF-I levels adjusted for 5-year age groups, gender and IGF-I binding protein 3 levels (linear regression, coefficient±s.e. for FTO AA genotype:-8.6±2.8; P=0.002). Further adjustments for obesity and diabetes did not suspend this association (coefficient:-7.8; P=0.005). As expected, the FTO AA genotype effect on BMI was reduced from 0.76 to 0.62 kg m(-2) by including IGF-I. No relationship between FTO and IGF-I levels was found in subjects aged 55 years or older (-2.7±2.4; P=0.260 for FTO AA genotype adjusted for age, gender and IGF-I binding protein 3 levels).
We propose that the GH-IGF-I axis is a mediator for the relationship between FTO and BMI.
肥胖相关基因（FTO）的风险等位基因不仅与体重指数（BMI）值的增加有关，还与死亡率有关。人们推测，FTO 基因的细胞效应影响大多数器官，尤其是当它们受到各种疾病侵袭时，维持或再生适当功能的能力。FTO 在下丘脑和垂体中高度表达。已知生长激素（GH）分泌减少会导致老年受试者瘦体重减少。
我们假设 rs9926289 与胰岛素样生长因子（IGF）-I 有关。
使用来自德国东北部基于人群的波罗的海健康研究的横断面数据。
对于最终分析，有 3882 名年龄在 20-79 岁的受试者可用。
连续 IGF-I、根据有意义的年龄和性别特异性参考值定义的低 IGF-I 以及 BMI 作为观察指标。
在所有年龄组中，均发现 FTO 与 IGF-I 之间存在统计学显著关系。在年龄小于 55 岁的受试者中，FTO 风险等位基因的纯合子携带者表现出较低的血清 IGF-I 水平，调整了 5 岁年龄组、性别和 IGF-I 结合蛋白 3 水平（线性回归，FTO AA 基因型的系数±标准误：-8.6±2.8；P=0.002）。进一步调整肥胖和糖尿病并未中止这种关联（系数：-7.8；P=0.005）。正如预期的那样，通过包括 IGF-I，FTO AA 基因型对 BMI 的影响从 0.76 降至 0.62 kg·m(-2)。在 55 岁或以上的受试者中，未发现 FTO 与 IGF-I 水平之间存在关系（FTO AA 基因型调整年龄、性别和 IGF-I 结合蛋白 3 水平后，为-2.7±2.4；P=0.260）。
我们提出 GH-IGF-I 轴是 FTO 与 BMI 之间关系的中介。
